A cure for Parkinson’s disease could be in the pipeline, scientists claim.
Experts believe they have finally cracked the secret behind a brain enzyme deemed responsible for the degenerative nerve condition.
PINK1 was flagged as a key player in preventing Parkinson’s in 2004, and multiple trials have delved into its actual role in the years since.
Dundee University researchers now believe they have worked out the 3D structure and inner workings of the enzyme.
The study, dubbed ‘vital’ and ‘fantastic’ by the medical community, could provide treatment for the symptoms of the condition, including shaking and rigidity.
Experts believe they have cracked the secret of a brain enzyme that is responsible for the degenerative nerve condition
Parkinson’s disease affects one in 500 people and around 127,000 people in the UK live with the condition. It is believed one million Americans also suffer.
High-profile victims include the actor Michael J Fox, who was diagnosed at the age of only 29, and the late boxing legend Muhammad Ali.
‘This knowledge is vital’
Professor David Dexter, deputy director of research at Parkinson’s UK, said: ‘The PINK1 gene was identified as a key player by researchers back in 2004.
‘Drugs that can switch the PINK1/parkin pathway back on may be able to slow, stop or even reverse nerve cell death, not only in people who have these rare inherited forms of the condition, but also those with non-inherited Parkinson’s.
‘This research, for the first time, gives us a view of what the PINK1 protein looks like and how changes in the gene can prevent the PINK1 protein working properly.
‘This knowledge is vital for developing drugs that can switch PINK1 back on, which has the potential to slow or even stop the progression of the condition, something current treatments are unable to do.’
A ‘fantastic’ step forward
Michael Dunn, head of the Wellcome Trust’s Genetics and Molecular Sciences team, said: ‘The PINK1 protein has been the focus of research all over the world, so this finding from the Dundee team is a fantastic step forward for the community.
‘If we understand the structure of this protein, which holds so many clues into what goes wrong in Parkinson’s, it may help us develop novel drugs to protect against this devastating disease.
‘Basic research is fundamental to understanding and treating many diseases and only by working in collaboration can we hope to make breakthroughs like this.’
What did they already know?
In early-onset Parkinson’s, a PINK1 mutation causes it to lose its protective function, leading to the degeneration of cells in the brain that control movement.
Previous research has shown that the main role of the PINK1 enzyme is to sense damage to the energy centres, or mitochondria, of cells.
This then switches on a protective pathway involving two key proteins, known as ubiquitin and Parkin, to reduce the damage.
But how this occurred was unknown – and finding a drug that could turn back on PINK1’s guard-role has long been a Holy Grail for Parkinson’s research.
What did they find?
The new study, published in the scientific journal eLife, offers hope of explaining exactly how the enzyme can be used in treatment.
PINK1 encodes a special class of enzyme, known as a kinase, that plays a critical role in protecting brain cells against stress.
The researchers said PINK1 has ‘unique control elements’ not found in other enzymes of its class that explain how it targets ubiquitin and Parkin.
Professor Daan van Aalten, who co-led the research, said the findings were a ‘transformative step’ on the way to a solution.
He said: ‘There has been great interest in directly targeting PINK1 as a potential therapy but without knowledge on the structure of the enzyme, this posed a major barrier.
‘Our work now provides a framework to undertake future studies directed at finding new drug like molecules that can target and activate PINK1.’